CpG motifs in bacterial DNA trigger direct B-cell activation

AM Krieg, AK Yi, S Matson, TJ Waldschmidt, GA Bishop… - Nature, 1995 - nature.com
AM Krieg, AK Yi, S Matson, TJ Waldschmidt, GA Bishop, R Teasdale, GA Koretzky
Nature, 1995nature.com
UNMETHYLATED CpG dinucleotides are more frequent in the gen-omes of bacteria and
viruses than of vertebrates. We report here that bacterial DNA and synthetic
oligodeoxynucleotides containing unmethylated CpG dinucleotides induce murine B cells to
proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by
simultaneous signals delivered through the antigen receptor. Optimal B-cell activation
requires a DNA motif in which an unmethylated CpG dinucleotide is flanked by two 5'purines …
Abstract
UNMETHYLATED CpG dinucleotides are more frequent in the gen-omes of bacteria and viruses than of vertebrates. We report here that bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides induce murine B cells to proliferate and secrete immunoglobulin in vitro and in vivo. This activation is enhanced by simultaneous signals delivered through the antigen receptor. Optimal B-cell activation requires a DNA motif in which an unmethylated CpG dinucleotide is flanked by two 5' purines and two 3' pyrimidines. Oligodeoxynucleotides containing this CpG motif induce more than 95% of all spleen B cells to enter the cell cycle. These data suggest a possible evolutionary link between immune defence based on the recognition of microbial DNA and the phenomenon of 'CpG suppression' in vertebrates. The potent immune activation by CpG oligonucleotides has impli-cations for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.
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